Lymphoma is cancer of the lymphatic system, a network of lymph nodes, organs (including the spleen, thymus, and tonsils), and vessels that help make up the immune system. There are many different types of lymphoma, and they can be divided into two categories: Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The major difference between the two is the type of cells involved.


Generally speaking, HD is easier to treat than NHL. Lymphoma is easiest to treat in its early stages, when the cancer hasn't spread beyond the lymphatic system. Lymphoma that either spreads to the bone marrow or develops in the brain can be more difficult to treat.


HIV-infected people are at a slightly higher risk for developing NHL than non-HIV-infected people. NHL can also progress (get worse) faster in HIV-positive people and can be more difficult to treat. It is not clear if HIV-positive people are at a higher risk for developing HD. However, HD does occur in HIV-infected people and, because of underlying immune suppression, can progress faster and may be more difficult to treat.


A number of recent studies have found that fewer HIV-positive people are being diagnosed with lymphoma today than they were in the years before combination anti-HIV drug treatment became available. The risk of developing one of the more serious types of lymphoma – lymphoma of the brain (primary CNS lymphoma), for example – has dramatically decreased in recent years. However, some types of NHL – Burkitt's lymphoma, for example – have not decreased.


Lymphomas are more likely to occur in HIV-positive people with fewer than 200 T-cells; primary CNS lymphoma is more likely to occur in people with fewer than 100 T-cells. However, there have been reports of lymphoma occuring in HIV-positive people with higher T-cell counts.


While the cause of lymphoma is still not known, many researchers believe that environmental toxins – such as pesticides – can cause this form of cancer. The Epstein-Barr virus (EBV) has also been found to play a role in the development of lymphomas, particularly in HIV-infected people.


What are the symptoms of lymphoma?

Lymphomas generally cause tumors to develop somewhere within the lymphatic system. Sometimes these tumors can be felt or seen under the skin. Tumors can also occur deep within the body, sometimes inside an organ (usually either the gut, the bone marrow, the brain, or the liver). A number of symptoms are possible. These include an enlarged spleen, liver obstruction, rectal pain, irregular heartbeat, digestive problems, and internal bleeding. Very often, lymphoma causes fever, unexplained weight loss, and night sweats.


Lymphoma of the brain – called primary central nervous system (CNS) lymphoma – may cause any number of symptoms. These include problems focusing, paralysis affecting one side of the body, loss of ability to speak or understand language, confusion, sudden memory loss, and mania.


How is lymphoma diagnosed?

First, health-care providers will look for the source of any symptoms. Blood tests can be helpful (e.g., uric acid and LDH levels), as can an MRI, PET scans, computed tomography (CT), or gallium scanning. If a tumor is suspected, a biopsy will then be performed. During a biopsy, a sample of the tumor will be collected as a part of a surgical procedure and sent to a lab for analysis. A biopsy of the bone marrow and a spinal tap are often necessary to determine if the cancer has spread beyond the tumor. Treating the lymphoma depends on this information.


Both Hodgkin's disease and NHL are classified by the same categories of stages. Most lymphomas in HIV-positive people involve B-cells, as opposed to T-cells.

The stage of the lymphoma is very important and can help determine prognosis and the course of treatment. The four stages are:


Stage I: There is one cancer site. No bone marrow involvement.

Stage II: There are two sites; both are either above or below the diaphragm. No bone marrow involvement.

Stage III: There are sites above and below the diaphragm. No bone marrow involvement.

Stage IV: The bone marrow is effected or the cancer cells have spread outside the lymphatic system.


In Hodgkin's disease, staging is further classified by letters, which indicate:

B: the presence of fever, weight loss or night sweats

A: the absence of fever, weight loss or night sweats

E: the disease has spread to organs outside the lymph system


As for CNS lymphoma, brain biopsies are the best way to diagnose suspected cancer. However, these surgical procedures are risky and are not routinely performed on HIV-positive men and women. Nonetheless, CNS lymphoma can look a lot like toxoplasmosis, so it's important to determine the true source of the lesion in the brain. Spinal taps, bone marrow biopsies, and careful inspection of scans can do this in most cases.


How is lymphoma treated?

Treating lymphoma is an aggressive process. While treatment – which includes surgery, chemotherapy, and radiation – can cure the patient, it can also cause serious side effects and reduce quality of life. HIV-infected patients with relatively high T-cell counts (greater than 200), a low-stage form of lymphoma, less than 35 years of age, and no prior history of an AIDS-related problem stand the best chance of curing the lymphoma and surviving radiation and/or chemotherapy.


The standard treatments for lymphoma include:


Surgery: Removing the tumor by way of surgery is often performed. Surgical removal of a tumor often requires chemotherapy and/or radiation to improve success rates.


Radiation (radiotherapy): Radiation uses high-energy x-rays to kill cancer cells and shrink individual tumors. Early-stage lymphomas (Stages I and II) can often be treated using radiation alone. However, most HIV-related lymphomas are diagnosed in their late stages, thus requiring chemotherapy in combination with radiation. Large doses of whole-brain radiation is the standard therapy for CNS lymphoma, curing between 20% and 50% of all patients who undergo therapy.


Chemotherapy for NHL: Drug therapy for lymphoma almost always involves a combination of three or more chemotherapy compounds. For NHL, there are three generally recommended regimens. Here are the three most common regimens:


  • mBACOD: A combination of methotrexate, bleomycin, Adriamycin®, cyclophosphamide, Oncovin®, and dexamethasone. While standard doses of this combination are most effective, lower doses can be prescribed for HIV-positive patients with low T-cell counts to help maintain as much immune function as possible. A clinical trial has determined that lower-dose mBACOD is just as effective as standard-dose mBACOD in HIV-positive people with lymphoma. However, in order to get the maximum benefit from treatment, patients who have high T-cell counts (more than 200 cells) before starting chemotherapy are often given the full dose of mBACOD. 

  • CHOP: A combination of cyclophosphamide, hydroxydaunomycin (doxorubicin), Oncovin®, and prednisone. As with mBACOD, a low-dose version of this regimen has been established for HIV-infected NHL patients. However, one study found that low-dose CHOP is not as effective as standard-dose CHOP. 

  • CDE: A combination of cyclophosphamide, doxorubicin, and This combination is usually given over a four-day period through an intravenous (IV) line.

Rituxan (rituximab): This is a monoclonal antibody that circulates around the body and marks lymphoma cells for destruction by other immune system cells. It is still experimental in terms of treating HIV-related lymphomas and not all HIV-related lymphomas can be treated with rituximab. However, clinical trials involving non-HIV-positive people with certain types of lymphoma found that rituximab, combined with standard chemotherapy drugs, increased the chance of curing the cancer. It is administered through an IV line, much like chemotherapy.


Chemotherapy for HD: The most common combination regimen, called ABVD, includes Adriamycin®, bleomycin, vinblastine, and dacarbazine.

CNS lymphoma prevention (prophylaxis): If the lymphoma is found to be in a high stage (stage III or IV), patients are often encouraged to undergo therapy to prevent cancer cells from spreading to the brain. To do so, a drug called cytarabine (Ara-C) is infused directly into the brain or spinal column every week, usually for four weeks, either at the beginning or the end of NHL therapy. The drug is administered either through a shunt, or port, surgically implanted in the skull, or through an IV line placed into the spinal column every week.


Opportunistic infection prevention (prophylaxis): Chemotherapy can cause T-cells and other white blood cells to decrease. This can increase the risk of developing infections like Pneumocystis carinii pneumonia (PCP). It is recommended that all HIV-infected patients undergoing lymphoma chemotherapy, regardless of their pre-treatment T-cell counts, receive prophylaxis to prevent PCP (e.g., Bactrim/Septra).


Side-effect therapies: Chemotherapy can have a serious effect on white blood cell counts (WBCs) and red blood cell counts (RBCs). Luckily there are treatments available to help manage these two serious side effects during chemotherapy. For decreased WBCs, particularly the bacteria-fighting neutrophils, drugs called colony stimulating factors (Neupogen® and Leukine®) are usually started within days after chemotherapy is initiated to protect these important cells. As for decreased RBCs due to chemotherapy, which can cause anemia and fatigue, blood transfusions are sometimes recommended, along with the drugs leucovorin calcium (Leukovorin®) and/or epoetin-alfa (Procrit®).


Nausea is another common side effect of chemotherapy. Drugs used to help control nausea are available and are often given to patients during and after chemotherapy infusion. Combating nausea is a process of trial and error. Patients often have to try several different anti-nausea drugs before finding one that works for them. While not approved by the Food and Drug Administration, smoking marijuana has been said to be highly effective for nausea and increasing appetite


Can lymphoma be prevented?

No, not at the present time. Researchers are still trying to figure out which HIV-positive patients are at the highest risk for developing lymphoma, along with the underlying cause of this form of cancer. Once more research is generated, it is likely the preventative therapies will be tested and recommended.


Are there any experimental treatments?

Scientific research has produced some important information, much of which can be used to design and test new therapies. It is likely that new therapies will be combined with each other and standard chemotherapy and/or radiation to produce safer, more effective responses.


Here's a glimpse at experimental treatments in development:

Immunotherapy: This therapy uses components of the immune system to combat cancer. It includes cytokines – proteins produced by cells in the body – which stimulate immune cells to kill cancer cells. Vaccines are also being studied using the patient's own tumor cells to mount an immune response against the tumor.


Monoclonal antibodies: These drugs are created by fusing specific human cells with molecularly-engineered antibodies or treated cells from humans or mice. When these antibodies are injected into the patient, they bind to cancer cells to alert the immune system to destroy them.

Rituxan (rituximab) is an example of a monoclonal antibody. It is approved for certain types of lymphoma. However, it has not been approved specifically for HIV-related lymphomas, although it is currently being used by many doctors to treat HIV-positive patients with this form of cancer. Clinical trials are currently looking at the safety and effectiveness of rituximab in combination with standard chemotherapy combinations (e.g., CHOP). 


Stem cell transplants: This a type of therapy that is being studied in HIV-positive people whose lymphoma was initially treated but has returned. The first step involves collected stem cells – "mother" cells in the bone marrow that produce important red blood cells and white blood cells. Once these cells are collected, very high doses of chemotherapy are given to the patient to kill off all of the lymphoma cells in the body (this is always done in a hospital, under the close supervision of a doctor and a team of nurses). Because the high chemotherapy doses are very toxic, it kills healthy cells in the process. Thus, once the chemotherapy is finished, the stem cells are put back into the body to help the bone marrow begin the process of producing new healthy cells.


Gene therapy: In this approach, defective genes could be replaced, or cells carrying specific, engineered genes could be introduced into the body to reinstate a normal cycle of cell reproduction, growth and death.


Anti-angiogenesis therapy: Tumor cells obtain life-sustaining nutrients and oxygen by growing capillaries (small blood vessels) to existing blood vessels, a process called angiogenesis. Anti-angiogenesis therapy inhibits this process by starving the cancer cells and making them more sensitive to chemotherapy and other treatments.


If you would like to find out if you are eligible for any clinical trials that include new therapies for the treatment or prevention of lymphoma, visit, a site run by the U.S. National Institutes of Health. The site has information about all HIV-related clinical studies in the United States. For more info, you can call their toll-free number at 1-800-HIV-0440 (1-800-448-0440) or email

Last Revised: January 18, 2016